August 26, 2010

Uncommon Lung Adenocarcinoma Variants: a mini-review

There are five common types of adenocarcinoma (actually I would say four since "mixed" doesn't seem to me a specific 'type") recognized in the WHO classification of lung cancer. But this classification also includes five rare but distinctive variants: fetal adenocarcinoma, mucin-producing adencarcinomas (mucinous "colloid" adenocarcinoma, mucinous cystadenocarcinoma, and signet ring adenocarcinoma), and clear cell adenocarcinoma.

While rare to exceedingly rare as pure tumors, the variant patterns are important to be aware of because they occur much more commonly as a component of mixed type adenocarcinomas, are associated with particular clinicopathologic features, and often require the exclusion of a different primary site. Another challenging variant is the nonmucinous lung adenocarcinoma which resembles colorectal adenocarcinoma but I'll review this variant in another post. Hope you all find this of use.

Cribriform arrangements can be prominent and cells arranged in cords and ribbons with peripheral palisading also described.

The tubules are lined by "endometrioid" nonciliated pseudostratified columnar cells with frequent subnuclear or supranuclear vacuoles.

Structures resembling squamous morules as in endometrioid adenocarcinoma are often present and the nuclei in these foci often appear optically clear (nuclear pseudoinclusions) due to biotin accumulation.

Frequent mitoses. Variable necrosis--focal to extensive.

Low-grade and high-grade variants are recognized which differ significantly in clinical and histopathologic parameters:

The cytological and architectural criteria for differentiating these tumors are also similar to those in the ovary, except that invasion of surrounding lung is diagnosed as a mixed subtype of adenocarcinoma (for reasons I'm not quite clear but there it is).

The mucinous epithelium in all of these cystic lesions differ from the mucinous adenocarcinoma type in that these express CK7 but inconsistently express CK20 and TTF-1. These are quite rare and have been studied for MUC2 or CDX2.

Signet ring adenocarcinomas

Rare as a pure subtype and uncommon (around 2%) as a component of mixed adenocarcinomas.

Younger average age when predominant as a component compared to average age of lung cancer patients in general

Unlike the other subtypes, this variant is defined by cytology--the classic signet-ring morphology.

Over 95% of tumors express CK7 and over 80% express TTF-1 but are negative for CK20; also positive for CEA, MUC1 and MUC5AC--a staining profile that helps distinguish this as a primary lung tumor versus metastasis from breast, gastric and colon primaries.

This is the most aggressive mucinous-type lung adenocarcinoma.

Tumors with at least 50% signet-ring component have a poorer 5-year survival rate compared to the typical adenocarcinoma prognosis.

Clear cell adenocarcinoma

Extremely rare as a pure subtype--but over a third of mixed adenocarcinomas show at least some focal clear cell change.

Tumor cells form sheets with at least focal tubal formation (the latter required for diagnosis) and may form papillae.